Choroidal neovascularization is the development of new blood vessels in the vascular choroid, which is comprised of the choriocapillaris and larger choroidal vessels. The choriocapillaris, which is a collection of richly perfused sinusoids, is located adjacent to the retinal pigmented epithelium and Bruch's membrane in the eye. It provides vascular support to the outer retina, including the pigmented epithelium and photoreceptors. The choriocapillaris atrophies with age-related macular degeneration, retinitis pigmentosa, and after removal of choroidal neovascular membranes in exudative age-related macular degeneration, presumed ocular histoplasmosis syndrome, and high myopia and, thus, is believed to contribute to the poor vision associated with such conditions.
One possible cause of the atrophy of the choriocapillaris is the degeneration of the pigmented epithelium. Clinically, the degeneration of the pigmented epithelium has been observed to precede choriocapillaris atrophy. Experimental studies of the choriocapillaris, however, have been mixed. Some researchers have reported that selective destruction of the pigmented epithelium, such as by laser burns, administration of sodium iodate or debridement, have led to choriocapillaris atrophy (Henkind et al., Trans. Ophthal. Soc. U.K. 103: 444-447 (1983); Korte et al., Invest. Ophthalmol. Vis. Sci. 25: 1135-1145 (1984); and Heriot et al., Graefes Arch. Clinical Exp. Ophthalmol. 230: 91-100 (1992)), whereas other researchers have reported that such selective destruction has led to atrophy followed by regeneration and differentiation of the choriocapillaris (Korte et al., Int. Rev. Cytology 152: 223-263 (1994); Pollack et al., Acta Anat. 143: 151-159 (1992); Pollack et al., Invest. Ophthalmol. Vis. Sci. 31: 890-898 (1990); Mancini et al., Invest. Ophthalmol. Vis. Sci. 27: 336-345 (1986); and Bums et al., Curr. Eye Res. 9: 863-873 (1992)). Hereditary degeneration of the pigmented epithelium has been shown to cause loss of the choriocapillaris in the Royal College of Surgeon's rat (Caldwell, Curr. Eye Res. 8: 907-921 (1989); and May et al., Exp. Eye Res. 63: 75-84 (1996)). Accordingly, the mechanisms by which the retinal pigmented epithelium regulates and maintains the choriocapillaris are not well understood. However, atrophy of the choriocapillaris is suspected to lead to choroidal neovascularization.
Currently, choroidal neovascularization is most commonly identified by fluorescein angiography, alone or in combination with indocyanine-green angiography, and well-defined choroidal neovascular lesions are treated by laser photocoagulation. Unfortunately, laser photocoagulation does not prevent neovascularization from persisting or recurring. Sometimes, when choroidal neovascularization occurs in association with exudative age-related macular degeneration, the choroidal neovascular complex is surgically removed. However, such subretinal surgery is hazardous and is generally only considered in functionally blind patients.
Therefore, there remains a great need for a method for the effective prophylactic and therapeutic treatment of choroidal neovascularization. Accordingly, it is a principal object of the present invention to provide a method of prophylactically and therapeutically treating choroidal neovascularization, such as that resulting from macular degeneration, e.g., age-related macular degeneration, recurrent or persistent choroidal neovascularization associated with treatments such as laser photocoagulation, photodynamic therapy and surgical removal of choroidal neovascularization, and choroidal neovascularization due to histoplasmosis, pathological myopia and other conditions. This and other objects of the present invention will become apparent from the detailed description provided herein.